title: Role of PDZK1 protein in apical membrane expression of renal sodium-coupled phosphate transporters.
abstract: The sodium-dependent phosphate (Na/P(i)) transporters NaPi-2a and NaPi-2c play a major role in the renal reabsorption of P(i). The functional need for several transporters accomplishing the same role is still not clear. However, the fact that these transporters show differential regulation under dietary and hormonal stimuli suggests different roles in P(i) reabsorption. The pathways controlling this differential regulation are still unknown, but one of the candidates involved is the NHERF family of scaffolding PDZ proteins. We propose that differences in the molecular interaction with PDZ proteins are related with the differential adaptation of Na/P(i) transporters. Pdzk1(-/-) mice adapted to chronic low P(i) diets showed an increased expression of NaPi-2a protein in the apical membrane of proximal tubules but impaired up-regulation of NaPi-2c. These results suggest an important role for PDZK1 in the stabilization of NaPi-2c in the apical membrane. We studied the specific protein-protein interactions of Na/P(i) transporters with NHERF-1 and PDZK1 by FRET. FRET measurements showed a much stronger interaction of NHERF-1 with NaPi-2a than with NaPi-2c. However, both Na/P(i) transporters showed similar FRET efficiencies with PDZK1. Interestingly, in cells adapted to low P(i) concentrations, there were increases in NaPi-2c/PDZK1 and NaPi-2a/NHERF-1 interactions. The differential affinity of the Na/P(i) transporters for NHERF-1 and PDZK1 proteins could partially explain their differential regulation and/or stability in the apical membrane. In this regard, direct interaction between NaPi-2c and PDZK1 seems to play an important role in the physiological regulation of NaPi-2c.
authors.affiliation: Department of Medicine, University of Colorado, Aurora, Colorado 80045, USA.
authors.forename: Hector
authors.initials: H
authors.lastname: Giral
authors.forename: Luca
authors.initials: L
authors.lastname: Lanzano
authors.forename: Yupanqui
authors.initials: Y
authors.lastname: Caldas
authors.forename: Judith
authors.initials: J
authors.lastname: Blaine
authors.forename: Jill W
authors.initials: JW
authors.lastname: Verlander
authors.forename: Tim
authors.initials: T
authors.lastname: Lei
authors.forename: Enrico
authors.initials: E
authors.lastname: Gratton
authors.forename: Moshe
authors.initials: M
authors.lastname: Levi
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D016764:Cell Polarity; D031541:Fluorescence Resonance Energy Transfer; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D007668:Kidney; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D050608:Sodium-Phosphate Cotransporter Proteins / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C514896:PDZK1 protein, mouse; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; D050608:Sodium-Phosphate Cotransporter Proteins; C093376:sodium-hydrogen exchanger regulatory factor